JP2007230961A - 1-fluoro-1,1-bis(phenylsulfonyl)methane and its manufacturinging method - Google Patents
1-fluoro-1,1-bis(phenylsulfonyl)methane and its manufacturinging method Download PDFInfo
- Publication number
- JP2007230961A JP2007230961A JP2006057330A JP2006057330A JP2007230961A JP 2007230961 A JP2007230961 A JP 2007230961A JP 2006057330 A JP2006057330 A JP 2006057330A JP 2006057330 A JP2006057330 A JP 2006057330A JP 2007230961 A JP2007230961 A JP 2007230961A
- Authority
- JP
- Japan
- Prior art keywords
- bis
- methane
- fluoro
- mmol
- arylsulfonyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 8
- TUZGMBZILYZZRU-UHFFFAOYSA-N [benzenesulfonyl(fluoro)methyl]sulfonylbenzene Chemical compound C=1C=CC=CC=1S(=O)(=O)C(F)S(=O)(=O)C1=CC=CC=C1 TUZGMBZILYZZRU-UHFFFAOYSA-N 0.000 title claims description 11
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims abstract description 56
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 4
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 3
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 27
- 150000001875 compounds Chemical class 0.000 abstract description 8
- 238000004519 manufacturing process Methods 0.000 abstract 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 53
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 239000000243 solution Substances 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000004440 column chromatography Methods 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 235000019270 ammonium chloride Nutrition 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- -1 monofluoromethyl group Chemical group 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 238000003756 stirring Methods 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 238000007069 methylation reaction Methods 0.000 description 8
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 8
- QBMBQMKZGFOAHR-DARPEHSRSA-N 1-[(e)-4,4-bis(benzenesulfonyl)-4-fluoro-3-[4-(2-methylpropyl)phenyl]but-1-enyl]-4-(2-methylpropyl)benzene Chemical compound C1=CC(CC(C)C)=CC=C1\C=C\C(C(F)(S(=O)(=O)C=1C=CC=CC=1)S(=O)(=O)C=1C=CC=CC=1)C1=CC=C(CC(C)C)C=C1 QBMBQMKZGFOAHR-DARPEHSRSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- OUQSAXROROGQEE-JOCHJYFZSA-N (s)-ipr-phox Chemical compound CC(C)[C@H]1COC(C=2C(=CC=CC=2)P(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 OUQSAXROROGQEE-JOCHJYFZSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000005688 desulfonylation reaction Methods 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Chemical compound [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
- CPRMKOQKXYSDML-UHFFFAOYSA-M rubidium hydroxide Chemical compound [OH-].[Rb+] CPRMKOQKXYSDML-UHFFFAOYSA-M 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000007259 addition reaction Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 150000001728 carbonyl compounds Chemical class 0.000 description 3
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 3
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 2
- GJYSYQQXHBPJRD-UHFFFAOYSA-N 1-(2-methylpropyl)-4-prop-1-enylbenzene Chemical compound CC=CC1=CC=C(CC(C)C)C=C1 GJYSYQQXHBPJRD-UHFFFAOYSA-N 0.000 description 2
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 2
- PHQQLRUNFPCGQC-UHFFFAOYSA-N 3,3-bis(benzenesulfonyl)-3-fluoro-2-[4-(2-methylpropyl)phenyl]propan-1-ol Chemical compound C1=CC(CC(C)C)=CC=C1C(CO)C(F)(S(=O)(=O)C=1C=CC=CC=1)S(=O)(=O)C1=CC=CC=C1 PHQQLRUNFPCGQC-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical compound CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- QCHNSJNRFSOCLJ-UHFFFAOYSA-N benzenesulfonylmethylsulfonylbenzene Chemical compound C=1C=CC=CC=1S(=O)(=O)CS(=O)(=O)C1=CC=CC=C1 QCHNSJNRFSOCLJ-UHFFFAOYSA-N 0.000 description 2
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 description 2
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 2
- CHDFNIZLAAFFPX-UHFFFAOYSA-N ethoxyethane;oxolane Chemical compound CCOCC.C1CCOC1 CHDFNIZLAAFFPX-UHFFFAOYSA-N 0.000 description 2
- QWLICVXJMVMDDQ-UHFFFAOYSA-N fluoro acetate Chemical compound CC(=O)OF QWLICVXJMVMDDQ-UHFFFAOYSA-N 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 238000007344 nucleophilic reaction Methods 0.000 description 2
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 2
- HVAMZGADVCBITI-UHFFFAOYSA-M pent-4-enoate Chemical class [O-]C(=O)CCC=C HVAMZGADVCBITI-UHFFFAOYSA-M 0.000 description 2
- XHFXMNZYIKFCPN-UHFFFAOYSA-N perchloryl fluoride Chemical compound FCl(=O)(=O)=O XHFXMNZYIKFCPN-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- NUMQCACRALPSHD-UHFFFAOYSA-N tert-butyl ethyl ether Chemical compound CCOC(C)(C)C NUMQCACRALPSHD-UHFFFAOYSA-N 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- SMBZJSVIKJMSFP-UHFFFAOYSA-N trifluoromethyl hypofluorite Chemical compound FOC(F)(F)F SMBZJSVIKJMSFP-UHFFFAOYSA-N 0.000 description 2
- QKZWXPLBVCKXNQ-UHFFFAOYSA-N (2-methoxyphenyl)-[2-[(2-methoxyphenyl)-phenylphosphanyl]ethyl]-phenylphosphane Chemical compound COC1=CC=CC=C1P(C=1C=CC=CC=1)CCP(C=1C(=CC=CC=1)OC)C1=CC=CC=C1 QKZWXPLBVCKXNQ-UHFFFAOYSA-N 0.000 description 1
- CQYMOICHLLQQAH-UHFFFAOYSA-N (r)-binaphane Chemical compound C1C2=CC=C3C=CC=CC3=C2C(C2=CC=CC=C2C=C2)=C2CP1C1=CC=CC=C1P(C1)CC2=CC=C(C=CC=C3)C3=C2C2=C1C=CC1=CC=CC=C21 CQYMOICHLLQQAH-UHFFFAOYSA-N 0.000 description 1
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 1
- SHJGEWDYIYRFSP-UHFFFAOYSA-N 1,3,5-tri(propan-2-yl)-2-[[2,4,6-tri(propan-2-yl)phenyl]sulfonylmethylsulfonyl]benzene Chemical compound CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1S(=O)(=O)CS(=O)(=O)C1=C(C(C)C)C=C(C(C)C)C=C1C(C)C SHJGEWDYIYRFSP-UHFFFAOYSA-N 0.000 description 1
- HZASUHYGVVTQEP-UHFFFAOYSA-N 1,3,5-trimethyl-2-[(2,4,6-trimethylphenyl)sulfonylmethylsulfonyl]benzene Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)CS(=O)(=O)C1=C(C)C=C(C)C=C1C HZASUHYGVVTQEP-UHFFFAOYSA-N 0.000 description 1
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 1
- JOCCGEZBHLDSQO-UHFFFAOYSA-N 1,3-bis[4-(2-methylpropyl)phenyl]prop-1-enyl acetate Chemical compound C1=CC(CC(C)C)=CC=C1CC=C(OC(C)=O)C1=CC=C(CC(C)C)C=C1 JOCCGEZBHLDSQO-UHFFFAOYSA-N 0.000 description 1
- OEDGFUGQLGKHEI-UHFFFAOYSA-N 1,3-ditert-butyl-5-[(3,5-ditert-butyl-4-methoxyphenyl)sulfonylmethylsulfonyl]-2-methoxybenzene Chemical compound C1=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=C1S(=O)(=O)CS(=O)(=O)C1=CC(C(C)(C)C)=C(OC)C(C(C)(C)C)=C1 OEDGFUGQLGKHEI-UHFFFAOYSA-N 0.000 description 1
- BUXRLPFUABMDCB-UHFFFAOYSA-N 1-[4-(2-methylpropyl)phenyl]propan-1-ol Chemical compound CCC(O)C1=CC=C(CC(C)C)C=C1 BUXRLPFUABMDCB-UHFFFAOYSA-N 0.000 description 1
- WEASZDNVBVZIJR-UHFFFAOYSA-N 1-bromo-2-[(2-bromophenyl)sulfonylmethylsulfonyl]benzene Chemical compound BrC1=CC=CC=C1S(=O)(=O)CS(=O)(=O)C1=CC=CC=C1Br WEASZDNVBVZIJR-UHFFFAOYSA-N 0.000 description 1
- GJTGIDYYCVVXRG-UHFFFAOYSA-N 1-bromo-3-[(3-bromophenyl)sulfonylmethylsulfonyl]benzene Chemical compound BrC1=CC=CC(S(=O)(=O)CS(=O)(=O)C=2C=C(Br)C=CC=2)=C1 GJTGIDYYCVVXRG-UHFFFAOYSA-N 0.000 description 1
- GNLWRDUYIDEDLG-UHFFFAOYSA-N 1-bromo-4-[(4-bromophenyl)sulfonylmethylsulfonyl]benzene Chemical compound C1=CC(Br)=CC=C1S(=O)(=O)CS(=O)(=O)C1=CC=C(Br)C=C1 GNLWRDUYIDEDLG-UHFFFAOYSA-N 0.000 description 1
- ATFJHZXDDVVTJJ-UHFFFAOYSA-N 1-butyl-4-prop-1-enylbenzene Chemical compound CCCCC1=CC=C(C=CC)C=C1 ATFJHZXDDVVTJJ-UHFFFAOYSA-N 0.000 description 1
- AWOQZDGIHNOBLG-UHFFFAOYSA-N 1-chloro-2-[(2-chlorophenyl)sulfonylmethylsulfonyl]benzene Chemical compound ClC1=CC=CC=C1S(=O)(=O)CS(=O)(=O)C1=CC=CC=C1Cl AWOQZDGIHNOBLG-UHFFFAOYSA-N 0.000 description 1
- UQLKRAFFXYZVBU-UHFFFAOYSA-N 1-chloro-4-[(4-chlorophenyl)sulfonylmethylsulfonyl]benzene Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)CS(=O)(=O)C1=CC=C(Cl)C=C1 UQLKRAFFXYZVBU-UHFFFAOYSA-N 0.000 description 1
- YKRHNBVOPORYLN-UHFFFAOYSA-N 1-ethyl-2-[(2-ethylphenyl)sulfonylmethylsulfonyl]benzene Chemical compound CCC1=CC=CC=C1S(=O)(=O)CS(=O)(=O)C1=CC=CC=C1CC YKRHNBVOPORYLN-UHFFFAOYSA-N 0.000 description 1
- UFHYXWKNIQRCES-UHFFFAOYSA-N 1-ethyl-3-[(3-ethylphenyl)sulfonylmethylsulfonyl]benzene Chemical compound CCC1=CC=CC(S(=O)(=O)CS(=O)(=O)C=2C=C(CC)C=CC=2)=C1 UFHYXWKNIQRCES-UHFFFAOYSA-N 0.000 description 1
- SDYJGSMJUIHMKT-UHFFFAOYSA-N 1-ethyl-4-[(4-ethylphenyl)sulfonylmethylsulfonyl]benzene Chemical compound C1=CC(CC)=CC=C1S(=O)(=O)CS(=O)(=O)C1=CC=C(CC)C=C1 SDYJGSMJUIHMKT-UHFFFAOYSA-N 0.000 description 1
- LWZRPYZXABAHFJ-UHFFFAOYSA-N 1-fluoro-4,6-bis(trifluoromethyl)pyridin-1-ium-2-sulfonate Chemical compound [O-]S(=O)(=O)C1=CC(C(F)(F)F)=CC(C(F)(F)F)=[N+]1F LWZRPYZXABAHFJ-UHFFFAOYSA-N 0.000 description 1
- PCUDTDNTOMIWJB-UHFFFAOYSA-N 1-fluoro-4,6-dimethylpyridin-1-ium-2-sulfonate Chemical compound CC1=CC(C)=[N+](F)C(S([O-])(=O)=O)=C1 PCUDTDNTOMIWJB-UHFFFAOYSA-N 0.000 description 1
- CZLMNRIAOUVXNU-UHFFFAOYSA-N 1-fluoro-4-methylpyridin-1-ium-2-sulfonate Chemical compound CC1=CC=[N+](F)C(S([O-])(=O)=O)=C1 CZLMNRIAOUVXNU-UHFFFAOYSA-N 0.000 description 1
- MEYCMYZKEHOPIF-UHFFFAOYSA-N 1-fluoro-5-(trifluoromethyl)pyridin-1-ium-2-sulfonate Chemical compound [O-]S(=O)(=O)C1=CC=C(C(F)(F)F)C=[N+]1F MEYCMYZKEHOPIF-UHFFFAOYSA-N 0.000 description 1
- AZKUIBOAKSSQTO-UHFFFAOYSA-N 1-methoxy-2-[(2-methoxyphenyl)sulfonylmethylsulfonyl]benzene Chemical compound COC1=CC=CC=C1S(=O)(=O)CS(=O)(=O)C1=CC=CC=C1OC AZKUIBOAKSSQTO-UHFFFAOYSA-N 0.000 description 1
- BVCFGPCNPFVMTP-UHFFFAOYSA-N 1-methoxy-3-[(3-methoxyphenyl)sulfonylmethylsulfonyl]benzene Chemical compound COC1=CC=CC(S(=O)(=O)CS(=O)(=O)C=2C=C(OC)C=CC=2)=C1 BVCFGPCNPFVMTP-UHFFFAOYSA-N 0.000 description 1
- QBTQTYZIRALXPA-UHFFFAOYSA-N 1-methoxy-4-[(4-methoxyphenyl)sulfonylmethylsulfonyl]benzene Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)CS(=O)(=O)C1=CC=C(OC)C=C1 QBTQTYZIRALXPA-UHFFFAOYSA-N 0.000 description 1
- DFNFBOZIKZXFRN-UHFFFAOYSA-N 1-methyl-2-[(2-methylphenyl)sulfonylmethylsulfonyl]benzene Chemical compound CC1=CC=CC=C1S(=O)(=O)CS(=O)(=O)C1=CC=CC=C1C DFNFBOZIKZXFRN-UHFFFAOYSA-N 0.000 description 1
- IVCKPVXMLYBDOM-UHFFFAOYSA-N 1-methyl-3-[(3-methylphenyl)sulfonylmethylsulfonyl]benzene Chemical compound CC1=CC=CC(S(=O)(=O)CS(=O)(=O)C=2C=C(C)C=CC=2)=C1 IVCKPVXMLYBDOM-UHFFFAOYSA-N 0.000 description 1
- XLOXYWLRAKCDQL-UHFFFAOYSA-N 1-methyl-4-[(4-methylphenyl)sulfonylmethylsulfonyl]benzene Chemical compound C1=CC(C)=CC=C1S(=O)(=O)CS(=O)(=O)C1=CC=C(C)C=C1 XLOXYWLRAKCDQL-UHFFFAOYSA-N 0.000 description 1
- LSMSSYSRCUNIFX-UHFFFAOYSA-N 1-methyl-4-prop-1-enylbenzene Chemical compound CC=CC1=CC=C(C)C=C1 LSMSSYSRCUNIFX-UHFFFAOYSA-N 0.000 description 1
- HIFFIDIWEOBZII-UHFFFAOYSA-N 1-prop-1-enyl-4-propylbenzene Chemical compound CCCC1=CC=C(C=CC)C=C1 HIFFIDIWEOBZII-UHFFFAOYSA-N 0.000 description 1
- SWOGZDBSWSFUIE-UHFFFAOYSA-N 1-tert-butyl-4-[(4-tert-butylphenyl)sulfonylmethylsulfonyl]benzene Chemical compound C1=CC(C(C)(C)C)=CC=C1S(=O)(=O)CS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 SWOGZDBSWSFUIE-UHFFFAOYSA-N 0.000 description 1
- BOMOHWDVLAJWEI-UHFFFAOYSA-N 2,4-dimethyl-1-prop-1-enylbenzene Chemical compound CC=CC1=CC=C(C)C=C1C BOMOHWDVLAJWEI-UHFFFAOYSA-N 0.000 description 1
- FYNXDGNCEBQLGC-KYJUHHDHSA-N 2,4-ditert-butyl-6-[[(1S,2S)-2-[(3,5-ditert-butyl-2-hydroxyphenyl)methylideneamino]cyclohexyl]iminomethyl]phenol Chemical compound CC(C)(C)C1=CC(C(C)(C)C)=CC(C=N[C@@H]2[C@H](CCCC2)N=CC=2C(=C(C=C(C=2)C(C)(C)C)C(C)(C)C)O)=C1O FYNXDGNCEBQLGC-KYJUHHDHSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- VTBGENTZANWBTA-UHFFFAOYSA-N 2-prop-1-enylnaphthalene Chemical compound C1=CC=CC2=CC(C=CC)=CC=C21 VTBGENTZANWBTA-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- PZVVUAIULJGRJE-UHFFFAOYSA-N 3-phenylprop-1-enyl acetate Chemical compound CC(=O)OC=CCC1=CC=CC=C1 PZVVUAIULJGRJE-UHFFFAOYSA-N 0.000 description 1
- BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- BNMZNFDZDSXYHM-UHFFFAOYSA-N CCCCCCCCC1=CC=C(C=CC)C=C1 Chemical compound CCCCCCCCC1=CC=C(C=CC)C=C1 BNMZNFDZDSXYHM-UHFFFAOYSA-N 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- 235000001258 Cinchona calisaya Nutrition 0.000 description 1
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- FCSHMCFRCYZTRQ-UHFFFAOYSA-N N,N'-diphenylthiourea Chemical compound C=1C=CC=CC=1NC(=S)NC1=CC=CC=C1 FCSHMCFRCYZTRQ-UHFFFAOYSA-N 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229910003074 TiCl4 Inorganic materials 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- RAIPGNPEEVDMSP-QURGRASLSA-N [(e)-4,4-bis(benzenesulfonyl)-4-fluoro-3-phenylbut-1-enyl]benzene Chemical compound C=1C=CC=CC=1S(=O)(=O)C(S(=O)(=O)C=1C=CC=CC=1)(F)C(C=1C=CC=CC=1)\C=C\C1=CC=CC=C1 RAIPGNPEEVDMSP-QURGRASLSA-N 0.000 description 1
- RZZDRSHFIVOQAF-UHFFFAOYSA-N [4-(5-diphenylphosphanyl-1,3-benzodioxol-4-yl)-1,3-benzodioxol-5-yl]-diphenylphosphane Chemical compound C=12OCOC2=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1C1=C2OCOC2=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RZZDRSHFIVOQAF-UHFFFAOYSA-N 0.000 description 1
- WDJHALXBUFZDSR-UHFFFAOYSA-N acetoacetic acid Chemical compound CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 1
- RBYGDVHOECIAFC-UHFFFAOYSA-L acetonitrile;palladium(2+);dichloride Chemical compound [Cl-].[Cl-].[Pd+2].CC#N.CC#N RBYGDVHOECIAFC-UHFFFAOYSA-L 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- WXNOJTUTEXAZLD-UHFFFAOYSA-L benzonitrile;dichloropalladium Chemical compound Cl[Pd]Cl.N#CC1=CC=CC=C1.N#CC1=CC=CC=C1 WXNOJTUTEXAZLD-UHFFFAOYSA-L 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical group C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- RRSCGNXXNRAXJC-UHFFFAOYSA-N bis(4-methylphenyl)phosphane Chemical compound C1=CC(C)=CC=C1PC1=CC=C(C)C=C1 RRSCGNXXNRAXJC-UHFFFAOYSA-N 0.000 description 1
- QKLWAMMQKBOTCD-UHFFFAOYSA-N butane;diphenylphosphane Chemical compound CCCC.C=1C=CC=CC=1PC1=CC=CC=C1 QKLWAMMQKBOTCD-UHFFFAOYSA-N 0.000 description 1
- OPIDHLGPELJSIO-UHFFFAOYSA-M cesium;hydron;difluoride Chemical compound [H+].[F-].[F-].[Cs+] OPIDHLGPELJSIO-UHFFFAOYSA-M 0.000 description 1
- FWXAUDSWDBGCMN-ZEQRLZLVSA-N chiraphos Chemical compound C=1C=CC=CC=1P([C@@H](C)[C@H](C)P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 FWXAUDSWDBGCMN-ZEQRLZLVSA-N 0.000 description 1
- AVPBPSOSZLWRDN-UHFFFAOYSA-M chloropalladium(1+);methanidylbenzene;triphenylphosphane Chemical compound [Pd+]Cl.[CH2-]C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 AVPBPSOSZLWRDN-UHFFFAOYSA-M 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000006104 desulfonylation Effects 0.000 description 1
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- HASCQPSFPAKVEK-UHFFFAOYSA-N dimethyl(phenyl)phosphine Chemical compound CP(C)C1=CC=CC=C1 HASCQPSFPAKVEK-UHFFFAOYSA-N 0.000 description 1
- OKUTYUNUKKPYJS-VWLOTQADSA-N diphenyl-[2-[(4r)-4-phenyl-4,5-dihydro-1,3-oxazol-2-yl]phenyl]phosphane Chemical compound C1([C@H]2N=C(OC2)C=2C(=CC=CC=2)P(C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=CC=C1 OKUTYUNUKKPYJS-VWLOTQADSA-N 0.000 description 1
- TWWJJVNUZQLCPD-UHFFFAOYSA-N diphenylphosphane;methane Chemical compound C.C=1C=CC=CC=1PC1=CC=CC=C1 TWWJJVNUZQLCPD-UHFFFAOYSA-N 0.000 description 1
- ONDPGJBEBGWAKI-UHFFFAOYSA-N diphenylphosphane;propane Chemical compound CCC.C=1C=CC=CC=1PC1=CC=CC=C1 ONDPGJBEBGWAKI-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- WDNMAVMEDYSCBN-UHFFFAOYSA-N hex-4-en-3-yl acetate Chemical compound CC(=O)OC(CC)C=CC WDNMAVMEDYSCBN-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- LGRLWUINFJPLSH-UHFFFAOYSA-N methanide Chemical compound [CH3-] LGRLWUINFJPLSH-UHFFFAOYSA-N 0.000 description 1
- DIHKMUNUGQVFES-UHFFFAOYSA-N n,n,n',n'-tetraethylethane-1,2-diamine Chemical compound CCN(CC)CCN(CC)CC DIHKMUNUGQVFES-UHFFFAOYSA-N 0.000 description 1
- RLKHFSNWQCZBDC-UHFFFAOYSA-N n-(benzenesulfonyl)-n-fluorobenzenesulfonamide Chemical compound C=1C=CC=CC=1S(=O)(=O)N(F)S(=O)(=O)C1=CC=CC=C1 RLKHFSNWQCZBDC-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- PENAXHPKEVTBLF-UHFFFAOYSA-L palladium(2+);prop-1-ene;dichloride Chemical compound [Pd+]Cl.[Pd+]Cl.[CH2-]C=C.[CH2-]C=C PENAXHPKEVTBLF-UHFFFAOYSA-L 0.000 description 1
- ULYNIEUXPCUIEL-UHFFFAOYSA-L palladium(2+);triethylphosphane;dichloride Chemical compound [Cl-].[Cl-].[Pd+2].CCP(CC)CC.CCP(CC)CC ULYNIEUXPCUIEL-UHFFFAOYSA-L 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- JKDRQYIYVJVOPF-FDGPNNRMSA-L palladium(ii) acetylacetonate Chemical compound [Pd+2].C\C([O-])=C\C(C)=O.C\C([O-])=C\C(C)=O JKDRQYIYVJVOPF-FDGPNNRMSA-L 0.000 description 1
- XDASSWBZWFFNPX-UHFFFAOYSA-N palladium(ii) cyanide Chemical compound [Pd+2].N#[C-].N#[C-] XDASSWBZWFFNPX-UHFFFAOYSA-N 0.000 description 1
- QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 1
- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
- FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 229960000948 quinine Drugs 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000012363 selectfluor Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/14—Sulfones; Sulfoxides having sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
本発明は、モノフルオロメチル化に有用な新規１−フルオロ−１，１−ビス（アリールスルホニル）メタンおよびその製造法に関する。 The present invention relates to a novel 1-fluoro-1,1-bis (arylsulfonyl) methane useful for monofluoromethylation and a process for producing the same.
フルオロ化合物は、医薬品として有用な生理活性物質において、特長ある性能を付加するものとして重要である。これまでエノラートなど活性化された部位でのモノフルオロ化、ハロゲンなどに対する置換反応などでのモノフルオロ化反応は知られていたが、モノフルオロメチル化反応は知られていない。 Fluoro compounds are important as physiologically active substances useful as pharmaceuticals, as they add characteristic performance. So far, monofluorination reaction at an activated site such as enolate and monofluorination reaction such as substitution reaction with halogen has been known, but monofluoromethylation reaction is not known.
本発明はモノフルオロメチル化に有用な新規１−フルオロ−１，１−ビス（アリールスルホニル）メタンおよびその製造法を提供することを課題とする。 An object of the present invention is to provide a novel 1-fluoro-1,1-bis (arylsulfonyl) methane useful for monofluoromethylation and a process for producing the same.
本発明者は、効率的なモノフルオロメチル化試薬を開発しようと鋭意研究した結果、1-フルオロ−１，１−ビス（アリールスルホニル)メタンを見いだしたものである。
すなわち、本発明は、下記式（１）で表されるビス（アリールスルホニル）メタンを
（ＡｒＳＯ２）２ＣＨ２（１）
（Ａｒは置換または無置換フェニル基、ナフチル基を表す）
塩基と処理し、ついで、フッ素化試薬を加えることによる下記式（２）で表されるフルオロビス（アリールスルホニル）メタンの製造法
（ＡｒＳＯ２）２ＣＨＦ（２）
（Ａｒは前に同じ）
および、モノフルオロメチル方を製造するのに極めて有用な新規化合物である上記式（２）で表されるフルオロビス（アリールスルホニル）メタン（２）からなる。
As a result of intensive studies to develop an efficient monofluoromethylation reagent, the present inventor has found 1-fluoro-1,1-bis (arylsulfonyl) methane.
That is, the present invention provides bis (arylsulfonyl) methane represented by the following formula (1).
(ArSO 2 ) 2 CH 2 (1)
(Ar represents a substituted or unsubstituted phenyl group or naphthyl group)
A process for producing fluorobis (arylsulfonyl) methane represented by the following formula (2) by treating with a base and then adding a fluorinating reagent (ArSO 2 ) 2 CHF (2)
(Ar is the same as before)
And a fluorobis (arylsulfonyl) methane (2) represented by the above formula (2), which is a novel compound extremely useful for producing a monofluoromethyl group.
本発明の化合物はモノフルオロメチル化試薬として用いることができる。 The compounds of the present invention can be used as monofluoromethylating reagents.
以下に本発明を詳しく説明する。 The present invention is described in detail below.
フルオロビス（アリールスルホニル）メタン（２）はビス（アリールスルホニル）メタンを塩基と処理し、カルボアニオンを生成し、ついでフッ素化試薬と反応させることにより得ることができる。塩基としては、K2O3, Li2CO3, Na2CO3, NaHCO3, NaOH, KOH, RbOH, CsOH, Cs2CO3, NaH, KHなどが好適に用いられる。塩基はビス（アリールスルホニル）メタンに対して１〜１０当量用いればよい。フッ素化試薬としては、N-フルオロベンゼンスルホンイミド、N-フルオロ-N-メチル-P-トルエンスルホンアミド、N-フルオロ-N'-クロロメチルトリエチレンジアミン ビス(テトラフルオロボラート) (SELECTFLUOR TM)、トリフルオロメチルハイポフルオライト（ＣＦ３ＯＦ）、アセチルハイポフルオライト（ＣＨ３ＣＯＯＦ）、フッ化過クロリル（ＣｌＯ３Ｆ）、硫酸セシウムフルオライト（ＣｓＳＯ４Ｆ）、1,1'-ジフルオロ-2,2'-ビピリジニウム ビス(テトラフルオロボラート)、Ｎ-フルオロ-４，６-ジメチルピリジニウム ２-スルホナート、Ｎ-フルオロ-４-メチルピリジニウム２-スルホナート、Ｎ-フルオロ-５-（トリフルオロメチル）ピリジニウム２-スルホナート、Ｎ-フルオロ-４，６-ビス（トリフルオロメチル）ピリジニウム２-スルホナートが挙げられる。フッ素化試薬は１〜１０当量が好適に用いられる。反応は有機溶媒中にて行なわれるが、塩化メチレン, クロロホルム, １，２−ジクロロエタン, トルエン, ベンゼン, ヘキサン、ペンタン, テトラヒドロフラン ジエチルエーテル, ｔ−ブチルエチルエーテル、ジメチルホルムアミド、ジメチルスルホキシド、アセとニトリル、メタノール、エタノールなどが挙げられる。 Fluorobis (arylsulfonyl) methane (2) can be obtained by treating bis (arylsulfonyl) methane with a base to produce a carbanion and then reacting with a fluorinating reagent. As the base, K 2 O 3 , Li 2 CO 3 , Na 2 CO 3 , NaHCO 3 , NaOH, KOH, RbOH, CsOH, Cs 2 CO 3 , NaH, KH and the like are preferably used. The base may be used in an amount of 1 to 10 equivalents relative to bis (arylsulfonyl) methane. Fluorinated reagents include N-fluorobenzenesulfonimide, N-fluoro-N-methyl-P-toluenesulfonamide, N-fluoro-N'-chloromethyltriethylenediamine bis (tetrafluoroborate) (SELECTFLUORTM), Trifluoromethyl hypofluorite (CF3OF), acetyl hypofluorite (CH3COOF), perchloryl fluoride (ClO3F), cesium fluoride fluoride (CsSO4F), 1,1'-difluoro-2,2'-bipyridinium bis (tetra Fluoroborate), N-fluoro-4,6-dimethylpyridinium 2-sulfonate, N-fluoro-4-methylpyridinium 2-sulfonate, N-fluoro-5- (trifluoromethyl) pyridinium 2-sulfonate, N-fluoro -4,6-bis (trifluoromethyl) pyridinium 2-sulfonate The The fluorinating reagent is preferably used in an amount of 1 to 10 equivalents. The reaction is carried out in an organic solvent, but methylene chloride, chloroform, 1,2-dichloroethane, toluene, benzene, hexane, pentane, tetrahydrofuran diethyl ether, t-butyl ethyl ether, dimethylformamide, dimethyl sulfoxide, ace and nitrile, Examples include methanol and ethanol.
フルオロビス（アリールスルホニル）メタン（２）はモノフルオロメチル化試薬として有用である。すなわち、（２）を塩基と処理し、カルボアニオンを生成し、ついで、下記に示す化合物（３）と求核反応することにより、フルオロビス（アリールスルホニル）メチル化された生成物（４）を得ることができる。（４）は、脱スルホニル化反応に供することによりモノフルオロメチル化生成物に簡便に変換できる。さらに注目すべきことは、フルオロビス（アリールスルホニル）メタン（２）から誘導されるカルボアニオンを、光学活性配位子を用いて各種触媒と反応させることにより、光学活性フルオロビス（アリールスルホニル）メチル化された生成物（４）を得ることができる点である。さらに、脱スルホニル化反応により光学活性モノフルオロメチル化化合物に導くことができる。すなわち、フルオロビス（アリールスルホニル）メタン（２）はそのカルボアニオンとして求核反応および脱スルホニル化反応により、光学活性モノフルオロメチル化化合物に誘導できる優れた試薬であり、従来全く知られていないフルオロメチルアニオン等価体とも称することができる。 Fluorobis (arylsulfonyl) methane (2) is useful as a monofluoromethylating reagent. That is, (2) is treated with a base to produce a carbanion, and then nucleophilic reaction with the compound (3) shown below yields a fluorobis (arylsulfonyl) methylated product (4). Obtainable. (4) can be easily converted into a monofluoromethylated product by subjecting it to a desulfonylation reaction. It should be further noted that optically active fluorobis (arylsulfonyl) methyl is obtained by reacting a carbanion derived from fluorobis (arylsulfonyl) methane (2) with various catalysts using an optically active ligand. It is a point which can obtain the quantified product (4). Furthermore, it can lead to an optically active monofluoromethylated compound by desulfonylation reaction. In other words, fluorobis (arylsulfonyl) methane (2) is an excellent reagent that can be derived into an optically active monofluoromethylated compound by nucleophilic reaction and desulfonylation reaction as its carbanion. It can also be referred to as a methyl anion equivalent.
ビス（アリールスルホニル）メタン（１）としては、ビス（フェニルスルホニル）メタン、ビス（４−メチルフェニルスルホニル）メタン、ビス（２−メチルフェニルスルホニル）メタン、ビス（３−メチルフェニルスルホニル）メタン、ビス（３−メトキシフェニルスルホニル）メタン、ビス（４−メトキシフェニルスルホニル）メタン、ビス（２−メトキシフェニルスルホニル）メタン、ビス（４−エチルフェニルスルホニル）メタン、ビス（３−エチルフェニルスルホニル）メタン、ビス（２−エチルフェニルスルホニル）メタン、ビス（２，４，６−トリメチルフェニルスルホニル）メタン、ビス（２，４，６−トリイソプロピルフェニルスルホニル）メタン、ビス（４−クロロフェニルスルホニル）メタン、ビス（３−クロロフェニルスルホニル）メタン、ビス（２−クロロフェニルスルホニル）メタン、ビス（４−ブロモフェニルスルホニル）メタン、ビス（３−ブロモフェニルスルホニル）メタン、ビス（２−ブロモフェニルスルホニル）メタン、ビス（４−ニトロフェニルスルホニル）メタン、ビス（４−ｔ−ブチルフェニルスルホニル）メタン、ビス（３，５−ジーｔ−ブチルー４−メトキシフェニルスルホニル）メタン等が挙げられるが、これらに限られるわけではない。 As bis (arylsulfonyl) methane (1), bis (phenylsulfonyl) methane, bis (4-methylphenylsulfonyl) methane, bis (2-methylphenylsulfonyl) methane, bis (3-methylphenylsulfonyl) methane, bis (3-methoxyphenylsulfonyl) methane, bis (4-methoxyphenylsulfonyl) methane, bis (2-methoxyphenylsulfonyl) methane, bis (4-ethylphenylsulfonyl) methane, bis (3-ethylphenylsulfonyl) methane, bis (2-ethylphenylsulfonyl) methane, bis (2,4,6-trimethylphenylsulfonyl) methane, bis (2,4,6-triisopropylphenylsulfonyl) methane, bis (4-chlorophenylsulfonyl) methane, bis (3 -Chlorofe Rusulfonyl) methane, bis (2-chlorophenylsulfonyl) methane, bis (4-bromophenylsulfonyl) methane, bis (3-bromophenylsulfonyl) methane, bis (2-bromophenylsulfonyl) methane, bis (4-nitrophenyl) Examples include, but are not limited to, sulfonyl) methane, bis (4-t-butylphenylsulfonyl) methane, bis (3,5-di-t-butyl-4-methoxyphenylsulfonyl) methane, and the like.
化合物（３）の例としては、アリル化合物、カルボニル化合物、a,b−不飽和カルボニル化合物、イミン類、ハロゲン化アルカンなどが挙げられる。具体的には、置換されていても良いアリルアセタート化合物が挙げられ、１−アセトキシー１，３，−ジフェニルプロペン、１−アセトキシー１，３，−ビス（４−イソブチルフェニル）プロペン、１−アセトキシー１，３，−ビス（４−イソブチルフェニル）プロペン、１−アセトキシー１，３，−ビス（４−イソブチルフェニル）プロペン、１−アセトキシー１，３，−ビス（４−メチルフェニル）プロペン、１−アセトキシー１，３，−ビス（４−ブチルフェニル）プロペン、１−アセトキシー１，３，−ビス（４−プロピルフェニル）プロペン、１−アセトキシー１，３，−ビス（４−オクチルフェニル）プロペン、１−アセトキシー１，３，−ビス（２，４−ジメチルフェニル）プロペン、１−アセトキシー１，３，−ジ（１−ナフチル）プロペン、１−アセトキシー１，３，−ジ（２−ナフチル）プロペン、１−アセトキシー３―フェニルプロペン、４−アセトキシヘキスー２−エン等が好適なアリルアセタート類として挙げられるが、もとよりこれらに限られることはない。 Examples of the compound (3) include allyl compounds, carbonyl compounds, a, b-unsaturated carbonyl compounds, imines, and halogenated alkanes. Specific examples include optionally substituted allyl acetate compounds such as 1-acetoxy-1,3, -diphenylpropene, 1-acetoxy-1,3, -bis (4-isobutylphenyl) propene, 1-acetoxy 1,3-bis (4-isobutylphenyl) propene, 1-acetoxy-1,3, -bis (4-isobutylphenyl) propene, 1-acetoxy-1,3, -bis (4-methylphenyl) propene, Acetoxy-1,3, -bis (4-butylphenyl) propene, 1-acetoxy-1,3, -bis (4-propylphenyl) propene, 1-acetoxy-1,3, -bis (4-octylphenyl) propene, 1 -Acetoxy-1,3, -bis (2,4-dimethylphenyl) propene, 1-acetoxy-1,3, -di (1-na Til) propene, 1-acetoxy-1,3, -di (2-naphthyl) propene, 1-acetoxy-3-phenylpropene, 4-acetoxyhex-2-ene and the like can be mentioned as suitable allyl acetates. It is not limited to these.
アリルアセタート化合物と触媒を反応させ、ついで、塩基存在下、フルオロビス（アリールスルホニル）メタン（２）と反応させ、フルオロビス（アリールスルホニル）メチル化された生成物（４）を得ることができる。ここで、触媒としては、パラジウム触媒が好適に用いられる。パラジウム触媒の例としては、アリルパラジウム(II)クロリド２量体、ビス（トリフェニルホスフィン）パラジウム(II)ジクロリド、トランスーベンジル（クロロ）ビス（トリフェニルホスフィン）パラジウム(II)、 ビス（アセトニトリル）ジクロロパラジウム(II)、ビス（ベンゾニトリル）パラジウム(II) クロリド、ビス（トリフェニルホスフィン）パラジウム(II)ジ酢酸、シスージクロロビス（ジメチルフェニルホスフィン）パラジウム(II)、ジクロロ（Ｎ，Ｎ，Ｎ‘，Ｎ’−テトラエチレンジアミン）パラジウム(II)、ジクロロビス（トリエチルホスフィン）パラジウム(II)、酢酸パラジウム(II)、パラジウム(II)アセチルアセトナート、パラジウム(II)シアニドなどが挙げられ、これらの触媒は通常、アキラルまたはキラルな配位子と共に用いられる。配位子はパラジウムに対して１当量用いればよい。例えばアキラル配位子としては、トリフェニルホスフィン、1,2-ビス（ジフェニルホスフィン）メタン、1,2-ビス（ジフェニルホスフィン）エタン、1,2-ビス（ジフェニルホスフィン）プロパン、1,2-ビス（ジフェニルホスフィン）ブタン、1,2-ビス（ジフェニルホスフィン）フェロセンが挙げられる。またキラル触媒としては、(R)-2-[2-(ジフェニルホスフィノ)フェニル]-4-フェニル-2-オキサゾリン, (R)-1'-ビナフチル-2.2'-ジフェニルホスフィン、[1,1'-ナフタレン]-2,2'-ジイルビス[ビス(4-メチルフェニル)ホスフィン、2,2'-イソプロピリデン[(4S)-4-フェニル-2-オキサゾリン] (Box-Ph), [4,4'-ビス-1,3-ベンゾジオキソール]-5,5'-ジイルlビス（ジフェニルホスフィン） (SEGPHOS), 1,2-ビス[(2S,5S)-2,5-ジメチルホスフォラノ]エタン(BPE), (R,R)-(-)-1,2-ビス{(R)-4,5-ジヒドロ-3H-ビナフト[1,2-c:2',1'-エ]ホスフィノ}ベンゼン (Binaphane), 1,2-エタンジイルビス[(2-メトキシフェニル)フェニルホスフィン(DIPAMP), [(1R,2S)-1,2-ジメチル-1,2-エタンジイル]ビス[ジフェニルホスフィン (CHIRAPHOS), (2R,3R)-ビシクロ[2.2.1]ヘプト-5-エン-2,3-ジイルビスジフェニルホスフィン(NORPHOS), [(2,2-ジメチル-1,3-ジオキソラン-4,5-ジイル)ビス(メチレン)]ビスジフェニルホスフィン (DIOP)などがあげられる。触媒量としては０．０１モル％から２０モル％の範囲で用いられるが、特に、０．１モル％から１０モル％の範囲で好適に用いられる。キラル配位子を使用すれば，キラルなフルオロビス（アリールスルホニル）メチル化された生成物（４）を得ることができる。 By reacting the allyl acetate compound with a catalyst and then reacting with fluorobis (arylsulfonyl) methane (2) in the presence of a base, a fluorobis (arylsulfonyl) methylated product (4) can be obtained. . Here, a palladium catalyst is suitably used as the catalyst. Examples of palladium catalysts include allyl palladium (II) chloride dimer, bis (triphenylphosphine) palladium (II) dichloride, trans-benzyl (chloro) bis (triphenylphosphine) palladium (II), bis (acetonitrile) Dichloropalladium (II), bis (benzonitrile) palladium (II) chloride, bis (triphenylphosphine) palladium (II) diacetic acid, cis-dichlorobis (dimethylphenylphosphine) palladium (II), dichloro (N, N, N ', N'-tetraethylenediamine) palladium (II), dichlorobis (triethylphosphine) palladium (II), palladium (II) acetate, palladium (II) acetylacetonate, palladium (II) cyanide, etc., and their catalysts Is usually used with achiral or chiral ligands . One equivalent of the ligand may be used with respect to palladium. For example, achiral ligands include triphenylphosphine, 1,2-bis (diphenylphosphine) methane, 1,2-bis (diphenylphosphine) ethane, 1,2-bis (diphenylphosphine) propane, 1,2-bis (Diphenylphosphine) butane, 1,2-bis (diphenylphosphine) ferrocene. Chiral catalysts include (R) -2- [2- (diphenylphosphino) phenyl] -4-phenyl-2-oxazoline, (R) -1'-binaphthyl-2.2'-diphenylphosphine, [1,1 '-Naphthalene] -2,2'-diylbis [bis (4-methylphenyl) phosphine, 2,2'-isopropylidene [(4S) -4-phenyl-2-oxazoline] (Box-Ph), [4, 4'-bis-1,3-benzodioxole] -5,5'-diyl-bis (diphenylphosphine) (SEGPHOS), 1,2-bis [(2S, 5S) -2,5-dimethylphosphor No] ethane (BPE), (R, R)-(-)-1,2-bis {(R) -4,5-dihydro-3H-binaphtho [1,2-c: 2 ', 1'-ethane ] Phosphino} benzene (Binaphane), 1,2-ethanediylbis [(2-methoxyphenyl) phenylphosphine (DIPAMP), [(1R, 2S) -1,2-dimethyl-1,2-ethanediyl] bis [diphenylphosphine ( CHIRAPHOS), (2R, 3R) -bicyclo [2.2.1] hept-5-ene-2,3-diylbisdiphenylphosphine (NORPHOS), [(2,2-dimethyl-1,3-dioxo Orchid-4,5-diyl) bis (methylene)] bisdiphenylphosphine (DIOP). The catalyst amount is used in the range of 0.01 mol% to 20 mol%, and particularly preferably in the range of 0.1 mol% to 10 mol%. If a chiral ligand is used, a chiral fluorobis (arylsulfonyl) methylated product (4) can be obtained.
また，塩基としては、K2O3, Li2CO3, Na2CO3, NaHCO3, NaOH, KOH, RbOH, CsOH, Cs2CO3, NaH, KHなどが好適に用いられる。反応は有機溶媒中にて行なわれるが、CH2Cl2, CHCl3, ClCH2CH2Cl, トルエン, ベンゼン, ヘキサン、ペンタン, テトラヒドロフラン ジエチルエーテル, ｔ−ブチルエチルエーテル、ジメチルホルムアミド、ジメチルスルホキシド、アセとニトリル、メタノール、エタノールなどが挙げられる。 As the base, K 2 O 3 , Li 2 CO 3 , Na 2 CO 3 , NaHCO 3 , NaOH, KOH, RbOH, CsOH, Cs 2 CO 3 , NaH, KH and the like are preferably used. The reaction is carried out in an organic solvent, but CH 2 Cl 2 , CHCl 3 , ClCH 2 CH 2 Cl, toluene, benzene, hexane, pentane, tetrahydrofuran diethyl ether, t-butyl ethyl ether, dimethylformamide, dimethyl sulfoxide, acetate. And nitrile, methanol, ethanol and the like.
反応は通常、-５０℃から８０℃の範囲で行なわれるが、特にー２０℃から４０℃の範囲で行なうのが好ましい。反応終了顔通常行なわれる方法により粗生成物を単離し、必要により、カラムクロマトグラフィーや蒸留、再結晶などの方法により、より純粋な生成物（４）を得ることができる。 The reaction is usually carried out in the range of −50 ° C. to 80 ° C., but it is particularly preferred to carry out in the range of −20 ° C. to 40 ° C. After completion of the reaction, the crude product is isolated by a method usually used, and if necessary, a purer product (4) can be obtained by a method such as column chromatography, distillation or recrystallization.
本発明よりなるフルオロビス（アリールスルホニル）メタン（２）は、キラルな触媒を用いることによりキラルなフルオロビス（アリールスルホニル）メチル化された生成物（４）を得ることができることにおいて他に類例のない特徴がある。さらに、フルオロビス（アリールスルホニル）メチル化された生成物（４）は、脱アリールスルホニル化することによりモノフルオロメチル化生成物に簡便に変換することができるという優れた特徴を有する。脱アリールスルホニル化は、例えば、マグネシウムとメタノール中にて反応させることにより好適に行なうことができる。さらに、この反応の際に、キラルなフルオロビス（アリールスルホニル）メチル化された生成物（４）の光学純度をほぼ落とすことなく、すなわち、ラセミ化を伴うことなくモノフルオロメチル化生成物に変換できることも特筆に値する。 The fluorobis (arylsulfonyl) methane (2) according to the present invention is another example in that a chiral fluorobis (arylsulfonyl) methylated product (4) can be obtained by using a chiral catalyst. There are no features. Furthermore, the fluorobis (arylsulfonyl) methylated product (4) has an excellent feature that it can be easily converted to a monofluoromethylated product by dearylsulfonylation. Dearylsulfonylation can be suitably performed by, for example, reacting magnesium in methanol. Furthermore, during this reaction, the chiral fluorobis (arylsulfonyl) methylated product (4) is converted to a monofluoromethylated product without substantially reducing the optical purity, ie without racemization. What you can do is also worthy of special mention.
酢酸アリル誘導体の他にも下記に示すフルオロビス（アリールスルホニル）メチル化された生成物を得ることができる。すなわち、α,β―不飽和カルボニル化合物へのβ―付加反応（反応式１）、ケトンまたはアルデヒドへの付加反応（反応式２）、イミンへの付加反応（反応式３）があげられる。これらの反応には延期が適宜用いられるが、例えば、トリエチルアミン、ジイソプロピルエチルアミン、, DBU, １，４−ジアザビシクロ[2,2,2]オクタン、DABCO、 ピリジン, ナトリウムメトキシド、ナトリウムエトキシド、ナトリウムｔ−ブトキシド、キニン、キニジン、シンコニン、シンコニジンがあげられる。触媒が好適に用いられるが、N-ベンジルシンコニジウムブロミド, (L)-プロリン, 1,3-ジフェニル-2-チオウレア, BINOL-Al 錯体 (ALB), BINOL-Ti錯体, Box-Ph,（S,S）−N,Ｎ‘−ビス（3,5−ジ-t-ブチルサリシリデン)-1,2-シクロヘキサンジアミン、K2CO3、TiCl4, SnCl4, AlCl3, Cu(OTf)2, MgCl2, NiClO4H2O, Pd(OAc)2、PPh3, dppe, dppp, dppbなどがあげられる。触媒、塩基と共に通常用いられる有機溶媒、例えば、CH2Cl2, CHCl3, ClCH2CH2Cl, Toluene, Benzene, Hexane, THF, Et2O, DMF, DMSO, CH3CNなどを用いて反応させればよい。 In addition to the allyl acetate derivative, the following fluorobis (arylsulfonyl) methylated product can be obtained. That is, a β-addition reaction to an α, β-unsaturated carbonyl compound (Reaction Formula 1), an addition reaction to a ketone or an aldehyde (Reaction Formula 2), and an addition reaction to an imine (Reaction Formula 3). Postponements are appropriately used in these reactions. For example, triethylamine, diisopropylethylamine, DBU, 1,4-diazabicyclo [2,2,2] octane, DABCO, pyridine, sodium methoxide, sodium ethoxide, sodium t -Butoxide, quinine, quinidine, cinchonine, cinchonidine. The catalyst is preferably used, but N-benzylcinchonidium bromide, (L) -proline, 1,3-diphenyl-2-thiourea, BINOL-Al complex (ALB), BINOL-Ti complex, Box-Ph, ( S, S) -N, N'-bis (3,5-di-t-butylsalicylidene) -1,2-cyclohexanediamine, K2CO3, TiCl4, SnCl4, AlCl3, Cu (OTf) 2, MgCl2, NiClO4H2O , Pd (OAc) 2, PPh3, dppe, dppp, dppb and the like. What is necessary is just to make it react using the organic solvent normally used with a catalyst and a base, for example, CH2Cl2, CHCl3, ClCH2CH2Cl, Toluene, Benzene, Hexane, THF, Et2O, DMF, DMSO, CH3CN etc.
こうして得られるフルオロビス（アリールスルホニル）メチル化生成物は、必要により脱スルホニルか反応を行うことにより、モノフルオロメチル化生成物に簡便に変換できる。 The fluorobis (arylsulfonyl) methylated product thus obtained can be easily converted to a monofluoromethylated product by desulfonylation or reaction if necessary.
以下に実施例を示し、本発明をさらに具体的に説明する。ただし、本発明は下記実施例に限定されるものではない。 The following examples illustrate the present invention more specifically. However, the present invention is not limited to the following examples.
1-フルオロ-1,1-ビス(フェニルスルホニル)メタンの合成
60% 油分散された水素化ナトリウム (205.3 mg, 0.833 mmol, 1.0 eq)のテトラヒドロフラン溶液40 mlを0 ℃に冷却した後に，ビス(フェニルスルホニル)メタン(241 mg, 0.813 mmol, 1.0 eq)を加え，室温で1時間攪拌する。得られた懸濁液を0 ℃でSelectfluor （N-フルオロ-N'-クロロメチルトリエチレンジアミン ビス(テトラフルオロボラート) (33.3 mg, 0.833 mmol, 1.0 eq)のアセトニトリル溶液50 mlに加え，室温で1 時間攪拌する。飽和塩化アンモニウム水溶液を加え，水層を塩化メチレンで抽出し，無水硫酸ナトリウムで乾燥させ，減圧下で溶媒を留去した後，カラムクロマトグラフィー (へキサン:塩化メチレン=2:8) で精製し，（２）を白色固体195 mg （57%）として得た。
1H NMR (200 MHz; CDCl3) δ 5.70 (1H, d, J = 45.8 Hz, CH), 7.55-7.65 (4H, m, Ar), 7.70-7.80 (2H, m, Ar), 7.95-8.05 (4H, d, Ar)
19F NMR (188 MHz; CDCl3)δ167.2 (d, J = 14.8 Hz)
MS (ESI-TOF) 314 (M+), 173 (M+ -SO2Ph), 141 (M+ -PhSO2CHF)
Synthesis of 1-fluoro-1,1-bis (phenylsulfonyl) methane
After cooling 40 ml of a 60% oil-dispersed sodium hydride solution (205.3 mg, 0.833 mmol, 1.0 eq) in tetrahydrofuran, bis (phenylsulfonyl) methane (241 mg, 0.813 mmol, 1.0 eq) was added. Stir at room temperature for 1 hour. The obtained suspension was added to 50 ml of acetonitrile solution of Selectfluor (N-fluoro-N'-chloromethyltriethylenediamine bis (tetrafluoroborate) (33.3 mg, 0.833 mmol, 1.0 eq)) at 0 ° C. Saturated aqueous ammonium chloride solution was added, the aqueous layer was extracted with methylene chloride, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and column chromatography (hexane: methylene chloride = 2: 8) to obtain (2) as a white solid 195 mg (57%).
1 H NMR (200 MHz; CDCl3) δ 5.70 (1H, d, J = 45.8 Hz, CH), 7.55-7.65 (4H, m, Ar), 7.70-7.80 (2H, m, Ar), 7.95-8.05 ( 4H, d, Ar)
19 F NMR (188 MHz; CDCl3) δ167.2 (d, J = 14.8 Hz)
MS (ESI-TOF) 314 (M + ), 173 (M + -SO2Ph), 141 (M + -PhSO2CHF)
1-フルオロ−１，１−ビス（フェニルスルホニル)メチル化反応
(4S)-2-(2-ジフェニルホスフィノフェニル)-4-イソプロピル-1,3-オキサゾリン (2.5 mg, 0.0067mmol, 5 mol%)と[Pd(C3H5)Cl]2 (1.2 mg, 0.0033 mmol, 2.5 mol%)と酢酸(2E)-1,3-ビス(4-イソブチルフェニル)-2-プロペニル (99.1 mg, 0.272 mmol, 2.0 eq)を塩化メチレン中，室温で15分間撹拌した。0 ℃に冷却した後に，1-フルオロ-1,1-ビス(フェニルスルホニル)メタン (42.6 mg, 0.136 mmol, 1.0 eq)とCs2CO3(87.8 mg, 0.270 mmol, 2.0 eq)を加え，0 ℃で60 時間攪拌した。飽和塩化アンモニウム水溶液を加え，水層を塩化メチレンで抽出し，無水硫酸ナトリウムで乾燥させ，減圧下で溶媒を留去した後，カラムクロマトグラフィー (へキサン:酢酸エチル=8:2) で精製し， (E)-4-フルオロ-1,3-ビス(4-イソブチルフェニル)-4,4-ビス(フェニルスルホニル)ブト-1-エンを黄色固体（77 mg 、91%, 98% ee）として得た。
HPLC (CHIRALCEL AD-H, Hexane/iPrOH=80:20, 1.0 ml/min, 10.0 min and 15.2 min)
1H NMR (200 MHz; CDCl3) δ 0.88 (12H, t, J = 5.8 Hz, CH3), 1.71-1.92 (2H, m, CH), 2.38 (2H, d, J = 7.2 Hz, CH2), 2.45 (2H, d, J = 7.0 Hz, CH2), 4.70 (1H, dd, J = 9.6, 14.5 Hz, CH=CH-CH), 6.46 (1H, d, J = 15.8 Hz, CH=CH-CH), 6.98-7.90 (19H, m, CH=CH-CH, Ar)
13C NMR (50 MHz; CDCl3)δ127.8 (d, J = 14.5 Hz) 14.3, 21.1, 30.1, 30.3, 45.0, 45.2. 51.1, 51.4, 60.3, 116.4, 119.0, 121.6, 121.7, 126.3, 128.1, 128.3, 128.5, 129.0, 130.0, 130.7, 132.4, 134.0, 134.4, 135.5, 136.0, 136.7, 141.0, 141.2
19F NMR (188 MHz; CDCl3)δ127.8 (d, J = 14.5 Hz)
1-Fluoro-1,1-bis (phenylsulfonyl) methylation reaction
(4S) -2- (2-Diphenylphosphinophenyl) -4-isopropyl-1,3-oxazoline (2.5 mg, 0.0067 mmol, 5 mol%) and [Pd (C 3 H 5 ) Cl] 2 (1.2 mg , 0.0033 mmol, 2.5 mol%) and acetic acid (2E) -1,3-bis (4-isobutylphenyl) -2-propenyl (99.1 mg, 0.272 mmol, 2.0 eq) in methylene chloride at room temperature for 15 minutes . After cooling to 0 ° C, 1-fluoro-1,1-bis (phenylsulfonyl) methane (42.6 mg, 0.136 mmol, 1.0 eq) and Cs 2 CO 3 (87.8 mg, 0.270 mmol, 2.0 eq) were added. Stir at 60 ° C. for 60 hours. Saturated aqueous ammonium chloride solution was added, the aqueous layer was extracted with methylene chloride, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography (hexane: ethyl acetate = 8: 2). , (E) -4-Fluoro-1,3-bis (4-isobutylphenyl) -4,4-bis (phenylsulfonyl) but-1-ene as a yellow solid (77 mg, 91%, 98% ee) Obtained.
HPLC (CHIRALCEL AD-H, Hexane / i PrOH = 80: 20, 1.0 ml / min, 10.0 min and 15.2 min)
1 H NMR (200 MHz; CDCl3) δ 0.88 (12H, t, J = 5.8 Hz, CH3), 1.71-1.92 (2H, m, CH), 2.38 (2H, d, J = 7.2 Hz, CH2), 2.45 (2H, d, J = 7.0 Hz, CH2), 4.70 (1H, dd, J = 9.6, 14.5 Hz, CH = CH-CH), 6.46 (1H, d, J = 15.8 Hz, CH = CH-CH) , 6.98-7.90 (19H, m, CH = CH-CH, Ar)
13 C NMR (50 MHz; CDCl3) δ127.8 (d, J = 14.5 Hz) 14.3, 21.1, 30.1, 30.3, 45.0, 45.2. 51.1, 51.4, 60.3, 116.4, 119.0, 121.6, 121.7, 126.3, 128.1, 128.3, 128.5, 129.0, 130.0, 130.7, 132.4, 134.0, 134.4, 135.5, 136.0, 136.7, 141.0, 141.2
19 F NMR (188 MHz; CDCl3) δ127.8 (d, J = 14.5 Hz)
1-フルオロ−１，１−ビス（フェニルスルホニル)メチル化反応
(4S)-2-(2-ジフェニルホスフィノフェニル)-4-イソプロピル-1,3-オキサゾリン(2.5 mg, 0.0067 mmol, 5 mol%)と[Pd(C3H5)Cl]2 (1.3 mg, 0.0036 mmol, 2.5 mol%)と酢酸(2E)-1,3-ビス(4-イソブチルフェニル)-2-プロペニル(50.2 mg, 0.138 mmol, 1.0 eq)をトリフルオロメチルベンゼン中，室温で15分間撹拌した。0 ℃に冷却した後に，1-フルオロ-1,1-ビス(フェニルスルホニル)メタン(47.9 mg, 0.152 mmol, 1.1 eq)とCs2CO3(49.3 mg, 0.151 mmol, 1.1 eq)を加え，0 ℃で10 時間攪拌した。飽和塩化アンモニウム水溶液を加え，水層を塩化メチレンで抽出し，無水硫酸ナトリウムで乾燥させ，減圧下で溶媒を留去した後，カラムクロマトグラフィー (へキサン:酢酸エチル=8:2) で精製し，(E)-4-フルオロ-1,3-ビス(4-イソブチルフェニル)-4,4-ビス(フェニルスルホニル)ブト-1-エンを黄色固体（12.0mg, 14%, 97% ee）として得た。
1-Fluoro-1,1-bis (phenylsulfonyl) methylation reaction
(4S) -2- (2-Diphenylphosphinophenyl) -4-isopropyl-1,3-oxazoline (2.5 mg, 0.0067 mmol, 5 mol%) and [Pd (C 3 H 5 ) Cl] 2 (1.3 mg , 0.0036 mmol, 2.5 mol%) and acetic acid (2E) -1,3-bis (4-isobutylphenyl) -2-propenyl (50.2 mg, 0.138 mmol, 1.0 eq) in trifluoromethylbenzene for 15 minutes at room temperature Stir. After cooling to 0 ° C, 1-fluoro-1,1-bis (phenylsulfonyl) methane (47.9 mg, 0.152 mmol, 1.1 eq) and Cs 2 CO 3 (49.3 mg, 0.151 mmol, 1.1 eq) were added. Stir at 10 ° C. for 10 hours. Saturated aqueous ammonium chloride solution was added, the aqueous layer was extracted with methylene chloride, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography (hexane: ethyl acetate = 8: 2). , (E) -4-fluoro-1,3-bis (4-isobutylphenyl) -4,4-bis (phenylsulfonyl) but-1-ene as a yellow solid (12.0 mg, 14%, 97% ee) Obtained.
1-フルオロ−１，１−ビス（フェニルスルホニル)メチル化反応
(4S)-2-(2-ジフェニルホスフィノフェニル)-4-イソプロピル-1,3-オキサゾリン (2.6 mg, 0.0070 mmol, 5 mol%)と[Pd(C3H5)Cl]2 (1.4 mg, 0.0038 mmol, 2.5 mol%)と酢酸(2E)-1,3-ビス(4-イソブチルフェニル)-2-プロペニル(50.8 mg, 0.139 mmol, 1.0 eq)をクロロホルム中，室温で15分間撹拌した。0 ℃に冷却した後に，1-フルオロ-1,1-ビス(フェニルスルホニル)メタン(47.4 mg, 0.151 mmol, 1.1 eq)とCs2CO3(49.5 mg, 0.152 mmol, 1.1 eq)を加え，0 ℃で24 時間攪拌した。飽和塩化アンモニウム水溶液を加え，水層を塩化メチレンで抽出し，無水硫酸ナトリウムで乾燥させ，減圧下で溶媒を留去した後，カラムクロマトグラフィー (へキサン:酢酸エチル=8:2) で精製し，(E)-4-フルオロ-1,3-ビス(4-イソブチルフェニル)-4,4-ビス(フェニルスルホニル)ブト-1-エンを黄色固体（5.8mg, 8%, 97% ee）として得た。
1-Fluoro-1,1-bis (phenylsulfonyl) methylation reaction
(4S) -2- (2-Diphenylphosphinophenyl) -4-isopropyl-1,3-oxazoline (2.6 mg, 0.0070 mmol, 5 mol%) and [Pd (C 3 H 5 ) Cl] 2 (1.4 mg , 0.0038 mmol, 2.5 mol%) and acetic acid (2E) -1,3-bis (4-isobutylphenyl) -2-propenyl (50.8 mg, 0.139 mmol, 1.0 eq) were stirred in chloroform at room temperature for 15 minutes. After cooling to 0 ° C, 1-fluoro-1,1-bis (phenylsulfonyl) methane (47.4 mg, 0.151 mmol, 1.1 eq) and Cs 2 CO 3 (49.5 mg, 0.152 mmol, 1.1 eq) were added. Stir at 24 ° C. for 24 hours. Saturated aqueous ammonium chloride solution was added, the aqueous layer was extracted with methylene chloride, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography (hexane: ethyl acetate = 8: 2). , (E) -4-fluoro-1,3-bis (4-isobutylphenyl) -4,4-bis (phenylsulfonyl) but-1-ene as a yellow solid (5.8 mg, 8%, 97% ee) Obtained.
1-フルオロ−１，１−ビス（フェニルスルホニル)メチル化反応
(4S)-2-(2-ジフェニルホスフィノフェニル)-4-イソプロピル-1,3-オキサゾリン (2.7 mg, 0.0072 mmol, 5 mol%)と[Pd(C3H5)Cl]2 (1.5 mg, 0.0041 mmol, 2.5 mol%)と酢酸(2E)-1,3-ビス(4-イソブチルフェニル)-2-プロペニル(81.9 mg, 0.225 mmol, 1.5 eq)をTHF中，室温で15分間撹拌した。0 ℃に冷却した後に，1-フルオロ-1,1-ビス(フェニルスルホニル)メタン(47.0 mg, 0.150 mmol, 1.0 eq)とNaH(9.2 mg, 0.230 mmol, 1.5 eq)のTHF溶液を滴下し，0 ℃で24 時間攪拌した。飽和塩化アンモニウム水溶液を加え，水層を塩化メチレンで抽出し，無水硫酸ナトリウムで乾燥させ，減圧下で溶媒を留去した後，カラムクロマトグラフィー (へキサン:酢酸エチル=8:2) で精製し，(E)-4-フルオロ-1,3-ビス(4-イソブチルフェニル)-4,4-ビス(フェニルスルホニル)ブト-1-エンを黄色固体（19.9mg, 21%, 95%ee）として得た。
1-Fluoro-1,1-bis (phenylsulfonyl) methylation reaction
(4S) -2- (2-Diphenylphosphinophenyl) -4-isopropyl-1,3-oxazoline (2.7 mg, 0.0072 mmol, 5 mol%) and [Pd (C 3 H 5 ) Cl] 2 (1.5 mg , 0.0041 mmol, 2.5 mol%) and acetic acid (2E) -1,3-bis (4-isobutylphenyl) -2-propenyl (81.9 mg, 0.225 mmol, 1.5 eq) were stirred in THF at room temperature for 15 minutes. After cooling to 0 ° C, a THF solution of 1-fluoro-1,1-bis (phenylsulfonyl) methane (47.0 mg, 0.150 mmol, 1.0 eq) and NaH (9.2 mg, 0.230 mmol, 1.5 eq) was added dropwise, The mixture was stirred at 0 ° C. for 24 hours. Saturated aqueous ammonium chloride solution was added, the aqueous layer was extracted with methylene chloride, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography (hexane: ethyl acetate = 8: 2). , (E) -4-fluoro-1,3-bis (4-isobutylphenyl) -4,4-bis (phenylsulfonyl) but-1-ene as a yellow solid (19.9mg, 21%, 95% ee) Obtained.
1-フルオロ−１，１−ビス（フェニルスルホニル)メチル化反応
2,2’-ビス(ジフェニルホスフィノ)-1,1’-ビナフチル (4.8 mg, 0.0077 mmol, 5 mol%)と[Pd(C3H5)Cl]2(1.6 mg, 0.0044 mmol, 2.5 mol%)と酢酸(2E)-1,3-ビス(4-イソブチルフェニル)-2-プロペニル(109.6 mg, 0.301 mmol, 2.0 eq)を塩化メチレン中，室温で15分間撹拌した。0 ℃に冷却した後に，1-フルオロ-1,1-ビス(フェニルスルホニル)メタン( 46.9 mg, 0.149 mmol, 1.0 eq)とCs2CO3 (98.4 mg, 0.302 mmol, 2.0 eq)を加え，0 ℃で48 時間攪拌した。飽和塩化アンモニウム水溶液を加え，水層を塩化メチレンで抽出し，無水硫酸ナトリウムで乾燥させ，減圧下で溶媒を留去した後，カラムクロマトグラフィー (へキサン:酢酸エチル=8:2) で精製し，(E)-4-フルオロ-1,3-ビス(4-イソブチルフェニル)-4,4-ビス(フェニルスルホニル)ブト-1-エンを黄色固体（80.3mg, 87%, 88% ee）として得た。
1-Fluoro-1,1-bis (phenylsulfonyl) methylation reaction
2,2'-bis (diphenylphosphino) -1,1'-binaphthyl (4.8 mg, 0.0077 mmol, 5 mol%) and [Pd (C 3 H 5 ) Cl] 2 (1.6 mg, 0.0044 mmol, 2.5 mol %) And acetic acid (2E) -1,3-bis (4-isobutylphenyl) -2-propenyl (109.6 mg, 0.301 mmol, 2.0 eq) were stirred in methylene chloride at room temperature for 15 minutes. After cooling to 0 ° C, 1-fluoro-1,1-bis (phenylsulfonyl) methane (46.9 mg, 0.149 mmol, 1.0 eq) and Cs 2 CO 3 (98.4 mg, 0.302 mmol, 2.0 eq) were added. Stir at 48 ° C. for 48 hours. Saturated aqueous ammonium chloride solution was added, the aqueous layer was extracted with methylene chloride, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography (hexane: ethyl acetate = 8: 2). , (E) -4-fluoro-1,3-bis (4-isobutylphenyl) -4,4-bis (phenylsulfonyl) but-1-ene as a yellow solid (80.3 mg, 87%, 88% ee) Obtained.
1-フルオロ−１，１−ビス（フェニルスルホニル)メチル化反応
(4S)-2-(2-ジフェニルホスフィノフェニル)-4-イソプロピル-1,3-オキサゾリン(3.6 mg, 0.0096 mmol, 5 mol%)と[Pd(C3H5)Cl]2 (1.8 mg, 0.0049 mmol, 2.5 mol%)と酢酸(2E)-1,3-ビス(4-イソブチルフェニル)-2-プロペニル(74.5 mg, 0.204 mmol, 1.0 eq)を塩化メチレン中，室温で15分間撹拌した。0 ℃に冷却した後に，1-フルオロ-1,1-ビス(フェニルスルホニル)メタン (70.6 mg, 0.225 mmol, 1.1 eq)とK2CO3(30.8 mg, 0.223 mmol, 1.1 eq)を加え，0 ℃で14 時間攪拌した。飽和塩化アンモニウム水溶液を加え，水層を塩化メチレンで抽出し，無水硫酸ナトリウムで乾燥させ，減圧下で溶媒を留去した後，カラムクロマトグラフィー (へキサン:酢酸エチル=8:2) で精製し，(E)-4-フルオロ-1,3-ビス(4-イソブチルフェニル)-4,4-ビス(フェニルスルホニル)ブト-1-エンを黄色固体（40 mg, 31%, 94% ee）として得た。
1-Fluoro-1,1-bis (phenylsulfonyl) methylation reaction
(4S) -2- (2-Diphenylphosphinophenyl) -4-isopropyl-1,3-oxazoline (3.6 mg, 0.0096 mmol, 5 mol%) and [Pd (C 3 H 5 ) Cl] 2 (1.8 mg , 0.0049 mmol, 2.5 mol%) and acetic acid (2E) -1,3-bis (4-isobutylphenyl) -2-propenyl (74.5 mg, 0.204 mmol, 1.0 eq) in methylene chloride at room temperature for 15 minutes . After cooling to 0 ° C, 1-fluoro-1,1-bis (phenylsulfonyl) methane (70.6 mg, 0.225 mmol, 1.1 eq) and K 2 CO 3 (30.8 mg, 0.223 mmol, 1.1 eq) were added. Stir at 14 ° C. for 14 hours. Saturated aqueous ammonium chloride solution was added, the aqueous layer was extracted with methylene chloride, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography (hexane: ethyl acetate = 8: 2). , (E) -4-fluoro-1,3-bis (4-isobutylphenyl) -4,4-bis (phenylsulfonyl) but-1-ene as a yellow solid (40 mg, 31%, 94% ee) Obtained.
1-フルオロ−１，１−ビス（フェニルスルホニル)メチル化反応
(4S)-2-(2-ジフェニルホスフィノフェニル)-4-イソプロピル-1,3-オキサゾリン(2.3 mg, 0.0062 mmol, 5 mol%)と[Pd(C3H5)Cl]2 (1.3 mg, 0.0036 mmol, 2.5 mol%)と酢酸(2E)-1,3-ビス(4-イソブチルフェニル)-2-プロペニル (50.6 mg, 0.139 mmol, 1.0 eq)をトルエン中，室温で15分間撹拌した。0 ℃に冷却した後に，1-フルオロ-1,1-ビス(フェニルスルホニル)メタン ( 48.2 mg, 0.153 mmol, 1.1 eq)とCs2CO3(49.8 mg, 0.153 mmol, 1.1 eq)を加え，0 ℃で8 時間攪拌した。飽和塩化アンモニウム水溶液を加え，水層を塩化メチレンで抽出し，無水硫酸ナトリウムで乾燥させ，減圧下で溶媒を留去した後，カラムクロマトグラフィー (へキサン:酢酸エチル=8:2) で精製し，(E)-4-フルオロ-1,3-ビス(4-イソブチルフェニル)-4,4-ビス(フェニルスルホニル)ブト-1-エンを黄色固体（8.8 mg, 10%, 96% ee）として得た。
1-Fluoro-1,1-bis (phenylsulfonyl) methylation reaction
(4S) -2- (2-Diphenylphosphinophenyl) -4-isopropyl-1,3-oxazoline (2.3 mg, 0.0062 mmol, 5 mol%) and [Pd (C 3 H 5 ) Cl] 2 (1.3 mg , 0.0036 mmol, 2.5 mol%) and acetic acid (2E) -1,3-bis (4-isobutylphenyl) -2-propenyl (50.6 mg, 0.139 mmol, 1.0 eq) were stirred in toluene at room temperature for 15 minutes. After cooling to 0 ° C, 1-fluoro-1,1-bis (phenylsulfonyl) methane (48.2 mg, 0.153 mmol, 1.1 eq) and Cs 2 CO 3 (49.8 mg, 0.153 mmol, 1.1 eq) were added. Stir at 8 ° C. for 8 hours. Saturated aqueous ammonium chloride solution was added, the aqueous layer was extracted with methylene chloride, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography (hexane: ethyl acetate = 8: 2). , (E) -4-fluoro-1,3-bis (4-isobutylphenyl) -4,4-bis (phenylsulfonyl) but-1-ene as a yellow solid (8.8 mg, 10%, 96% ee) Obtained.
1-フルオロ−１，１−ビス（フェニルスルホニル)メチル化反応
(E)-4-フルオロ-1,3-ジフェニル-4,4-ビス(フェニルスルホニル)ブト-1-エンの合成
(4S)-2-(2-ジフェニルホスフィノフェニル)-4-イソプロピル-1,3-オキサゾリン(3.5 mg, 0.00937 mmol, 5 mol%)と[Pd(C3H5)Cl]2 (1.8 mg, 0.0049 mmol, 2.5 mol%)と酢酸(E)-1,3-ジフェニルアリル (50.5 mg, 0.200 mmol, 1.0 eq)を1,2-ジクロロエタン中，室温で15分間撹拌した。0 ℃に冷却した後に，1-フルオロ-1,1-ビス(フェニルスルホニル)メタン （68.6 mg, 0.218 mmol, 1.1 eq)とCs2CO3(71.2 mg, 0.219 mmol, 1.1 eq)を加え，0 ℃で2 時間攪拌した。飽和塩化アンモニウム水溶液を加え，水層を塩化メチレンで抽出し，無水硫酸ナトリウムで乾燥させ，減圧下で溶媒を留去した後，カラムクロマトグラフィー (へキサン:塩化メチレン=3:7) で精製し，(E)-4-フルオロ-1,3-ジフェニル-4,4-ビス(フェニルスルホニル)ブト-1-エン（33.4mg, 33%, 91% ee）を白色固体として得た。
1H NMR (200 MHz; CDCl3) δ4.72 (1H, dd, J = 9.2, 14.5 Hz, CH=CH-CH), 6.49 (1H, d, J = 15.8 Hz, CH=CH-CH), 7.00-7.90 (21H, m, CH=CH-CH, Ar)
19F NMR (188 MHz; CDCl3)δ128.5 (d, J = 14.5 Hz)
1-Fluoro-1,1-bis (phenylsulfonyl) methylation reaction
Synthesis of (E) -4-fluoro-1,3-diphenyl-4,4-bis (phenylsulfonyl) but-1-ene
(4S) -2- (2-Diphenylphosphinophenyl) -4-isopropyl-1,3-oxazoline (3.5 mg, 0.00937 mmol, 5 mol%) and [Pd (C 3 H 5 ) Cl] 2 (1.8 mg , 0.0049 mmol, 2.5 mol%) and acetic acid (E) -1,3-diphenylallyl (50.5 mg, 0.200 mmol, 1.0 eq) were stirred in 1,2-dichloroethane at room temperature for 15 minutes. After cooling to 0 ° C, 1-fluoro-1,1-bis (phenylsulfonyl) methane (68.6 mg, 0.218 mmol, 1.1 eq) and Cs 2 CO 3 (71.2 mg, 0.219 mmol, 1.1 eq) were added. The mixture was stirred at ° C for 2 hours. Saturated aqueous ammonium chloride solution was added, the aqueous layer was extracted with methylene chloride, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography (hexane: methylene chloride = 3: 7). , (E) -4-fluoro-1,3-diphenyl-4,4-bis (phenylsulfonyl) but-1-ene (33.4 mg, 33%, 91% ee) was obtained as a white solid.
1 H NMR (200 MHz; CDCl3) δ4.72 (1H, dd, J = 9.2, 14.5 Hz, CH = CH-CH), 6.49 (1H, d, J = 15.8 Hz, CH = CH-CH), 7.00 -7.90 (21H, m, CH = CH-CH, Ar)
19 F NMR (188 MHz; CDCl3) δ128.5 (d, J = 14.5 Hz)
3-フルオロ-2-(4-イソブチルフェニル)-3,3-ビス(フェニルスルホニル)プロパン-1-オールの合成
(E)-4-フルオロ-1,3-ビス(4-イソブチルフェニル)-4,4-ビス(フェニルスルホニル)ブト-1-エン (5a, 506 mg, 0.818 mmol, 1.0 eq)のMeOH 20 ml, CH2Cl2 7 ml溶液を-78 ℃に冷却し，そこにオゾン発生装置で発生させたオゾンガスを30 min導入した後，5分間O2を導入し，過剰のオゾンを除いた。続いてNaBH4(93.1 mg, 2.49 mmol, 3.0 eq)を加え，2 hかけて室温まで昇温した。飽和塩化アンモニウム水溶液を加え，水層を塩化メチレンで抽出し，無水硫酸ナトリウムで乾燥させ，減圧下で溶媒を留去した後，カラムクロマトグラフィー (へキサン:酢酸エチル=6:4) で精製し，3-フルオロ-2-(4-イソブチルフェニル)-3,3-ビス(フェニルスルホニル)プロパン-1-オールを白色固体（393 mg, 98%）として得た。
1H NMR (200 MHz; CDCl3) δ 0.88 (6H, d, J= 6.6 Hz, CH3), 1.70-1.90 (1H, m, CH), 2.19 (1H, t, J = 6.2 Hz, OH), 2.39 (2H, d, J = 7.2 Hz, CH2), 3.95-4.10 (1H, m, CH), 4.42-4.60 (1H, m, CHH), 4.68-4.84 (1H, m, CHH), 6.90-7.10 (4H, m, Ar), 7.40-7.60 (4H, m, Ar), 7.60-7.80 (6H, m, Ar)
19F NMR (188 MHz; CDCl3)δ129.7 (d, J = 9.2 Hz)
Synthesis of 3-fluoro-2- (4-isobutylphenyl) -3,3-bis (phenylsulfonyl) propan-1-ol
(E) -4-Fluoro-1,3-bis (4-isobutylphenyl) -4,4-bis (phenylsulfonyl) but-1-ene (5a, 506 mg, 0.818 mmol, 1.0 eq) in MeOH 20 ml , CH 2 Cl 2 7 ml solution was cooled to -78 ° C, ozone gas generated by ozone generator was introduced for 30 min, then O 2 was introduced for 5 min to remove excess ozone. Subsequently, NaBH 4 (93.1 mg, 2.49 mmol, 3.0 eq) was added, and the temperature was raised to room temperature over 2 h. Saturated aqueous ammonium chloride solution was added, the aqueous layer was extracted with methylene chloride, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography (hexane: ethyl acetate = 6: 4). , 3-Fluoro-2- (4-isobutylphenyl) -3,3-bis (phenylsulfonyl) propan-1-ol was obtained as a white solid (393 mg, 98%).
1 H NMR (200 MHz; CDCl 3 ) δ 0.88 (6H, d, J = 6.6 Hz, CH 3 ), 1.70-1.90 (1H, m, CH), 2.19 (1H, t, J = 6.2 Hz, OH) , 2.39 (2H, d, J = 7.2 Hz, CH2), 3.95-4.10 (1H, m, CH), 4.42-4.60 (1H, m, CHH), 4.68-4.84 (1H, m, CHH), 6.90- 7.10 (4H, m, Ar), 7.40-7.60 (4H, m, Ar), 7.60-7.80 (6H, m, Ar)
19 F NMR (188 MHz; CDCl 3 ) δ129.7 (d, J = 9.2 Hz)
脱スルホニル化反応
マグネシウムリボン (707 mg, 29.1 mmol, 45.0 eq)のMeOH 5 ml溶液にCH2Br2を１滴，続いてTMSClを１滴加える。０℃に冷却した後，3-フルオロ-2-(4-イソブチルフェニル)-3,3-ビス(フェニルスルホニル)プロパン-1-オール (317 mg, 0.646 mmol, 1.0 eq)のMeOH 5 ml溶液を滴下する。0 ℃で2時間攪拌したのち，水を加えて反応を停止させ，１M HClで水溶液を酸性にする。水層を塩化メチレンで抽出し，無水硫酸ナトリウムで乾燥させ，減圧下で溶媒を留去した後，カラムクロマトグラフィー (へキサン:酢酸エチル=7:3) で精製し，3-フルオロ-2-(4-イソブチルフェニル)プロパン-1-オール（119 mg, 87%）を得た。
1H NMR (200 MHz; CDCl3) δ 0.90 (6H, d, J = 6.6 Hz, CH3), 1.55 (1H, br, OH), 1.74-1.95 (1H, m, CH), 2.44 (2H, d, J = 7.2 Hz, CH2), 3.05-3.30 (1H, dm, J= 19.8 Hz, CHCH2F), 4.69 (2H, dd, J = 5.6, 47.2 Hz, CH2F), 7.00-7.20 (4H, m, Ar)
19F NMR (188 MHz; CDCl3)δ 8.15 (dt, J = 19.8, 47.2 Hz)
MS (ESI-TOF) 210 (M+), 179 (M+ -CH2OH), 160 (M+-CH2OH, F)
Desulfonylation reaction
Add 1 drop of CH 2 Br 2 followed by 1 drop of TMSCl to a 5 ml solution of magnesium ribbon (707 mg, 29.1 mmol, 45.0 eq) in MeOH. After cooling to 0 ° C., a solution of 3-fluoro-2- (4-isobutylphenyl) -3,3-bis (phenylsulfonyl) propan-1-ol (317 mg, 0.646 mmol, 1.0 eq) in 5 ml of MeOH was added. Dripping. After stirring at 0 ° C. for 2 hours, water is added to quench the reaction, and the aqueous solution is acidified with 1M HCl. The aqueous layer was extracted with methylene chloride, dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography (hexane: ethyl acetate = 7: 3). (4-Isobutylphenyl) propan-1-ol (119 mg, 87%) was obtained.
1 H NMR (200 MHz; CDCl 3 ) δ 0.90 (6H, d, J = 6.6 Hz, CH 3 ), 1.55 (1H, br, OH), 1.74-1.95 (1H, m, CH), 2.44 (2H, d, J = 7.2 Hz, CH 2 ), 3.05-3.30 (1H, dm, J = 19.8 Hz, CHCH 2 F), 4.69 (2H, dd, J = 5.6, 47.2 Hz, CH 2 F), 7.00-7.20 (4H, m, Ar)
19 F NMR (188 MHz; CDCl 3 ) δ 8.15 (dt, J = 19.8, 47.2 Hz)
MS (ESI-TOF) 210 (M + ), 179 (M + -CH 2 OH), 160 (M + -CH 2 OH, F)
Claims (3)
（ＡｒＳＯ２）ＣＨ２（１）
（Ａｒは置換または無置換フェニル基、ナフチル基を表す）
塩基と処理し、ついで、フッ素化試薬を加えることによる下記式（２）で表されるフルオロビス（アリールスルホニル）メタンの製造法。
（ＡｒＳＯ２）ＣＨＦ（２）
（Ａｒは前に同じ） Bis (arylsulfonyl) methane represented by the following formula (1)
(ArSO 2 ) CH 2 (1)
(Ar represents a substituted or unsubstituted phenyl group or naphthyl group)
A process for producing fluorobis (arylsulfonyl) methane represented by the following formula (2) by treating with a base and then adding a fluorinating reagent.
(ArSO 2 ) CHF (2)
(Ar is the same as before)
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2006057330A JP4951754B2 (en) | 2006-03-03 | 2006-03-03 | Fluorobis (arylsulfonyl) methane and process for producing the same |
| US12/224,664 US7638654B2 (en) | 2006-03-03 | 2007-03-02 | 1-fluoro-1, 1-bis-(phenylsulfonyl)methane and production method thereof |
| PCT/JP2007/053997 WO2007100074A1 (en) | 2006-03-03 | 2007-03-02 | 1-fluoro-1,1-bis(phenylsulfonyl)methane and method for producing same |
| EP07737646A EP1992612A4 (en) | 2006-03-03 | 2007-03-02 | 1-fluoro-1,1-bis(phenylsulfonyl)methane and method for producing same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2006057330A JP4951754B2 (en) | 2006-03-03 | 2006-03-03 | Fluorobis (arylsulfonyl) methane and process for producing the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007230961A true JP2007230961A (en) | 2007-09-13 |
| JP4951754B2 JP4951754B2 (en) | 2012-06-13 |
Family
ID=38459169
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006057330A Expired - Fee Related JP4951754B2 (en) | 2006-03-03 | 2006-03-03 | Fluorobis (arylsulfonyl) methane and process for producing the same |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US7638654B2 (en) |
| EP (1) | EP1992612A4 (en) |
| JP (1) | JP4951754B2 (en) |
| WO (1) | WO2007100074A1 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009113362A1 (en) | 2008-03-10 | 2009-09-17 | セントラル硝子株式会社 | Method for producing oxygen-containing halogenated fluoride |
| WO2009147917A1 (en) | 2008-06-02 | 2009-12-10 | セントラル硝子株式会社 | Method for manufacturing oxygen-containing halogenated fluoride |
| WO2010100833A1 (en) * | 2009-03-02 | 2010-09-10 | 国立大学法人名古屋工業大学 | 2-fluoro-1,3-benzodithiol 1,1,3,3-tetraoxide derivatives, process for the preparation of same, and process for the preparation of monofluoromethyl-containing compounds using same |
| JP2015078135A (en) * | 2013-10-15 | 2015-04-23 | 東ソ−・エフテック株式会社 | 1-bromo-1-fluorobis(phenylsulfonyl)methane, manufacturing method thereof and manufacturing method of 1-fluorobis(phenylsulfonyl)methane using the same |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2632896B1 (en) | 2010-10-27 | 2017-03-15 | Hovione Inter Limited | Electrophilic reagents for monohalomethylation,their preparation and their uses |
| CN104530049B (en) * | 2014-12-09 | 2016-06-15 | 河南师范大学 | A kind of method synthesizing fluorine-containing acyclonucleosides analog |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6117530A (en) * | 1984-06-15 | 1986-01-25 | チバ‐ガイギー アクチエンゲゼルシヤフト | Manufacture of alpha,alpha-difluoroalkylphenyl ether and alpha-chloro-alpha-fluoroalkylphenyl ether and alpha-chloro-alpha-fluoroalkylphenyl ether derivative |
| JPH111468A (en) * | 1997-06-13 | 1999-01-06 | Mitsui Chem Inc | Production of diiodomethyl-p-toluylsulfone |
| JP2001348354A (en) * | 2000-06-05 | 2001-12-18 | Fuji Photo Film Co Ltd | Method for producing halomethane compound |
| JP2005511665A (en) * | 2001-11-29 | 2005-04-28 | ユニバーシティ・オブ・サザン・カリフォルニア | Preparation of fluorinated alkylsilanes mediated by magnesium |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4562280A (en) * | 1984-10-18 | 1985-12-31 | The Dow Chemical Company | Chloromethylation of deactivated aromatic compounds |
-
2006
- 2006-03-03 JP JP2006057330A patent/JP4951754B2/en not_active Expired - Fee Related
-
2007
- 2007-03-02 WO PCT/JP2007/053997 patent/WO2007100074A1/en active Application Filing
- 2007-03-02 EP EP07737646A patent/EP1992612A4/en not_active Withdrawn
- 2007-03-02 US US12/224,664 patent/US7638654B2/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6117530A (en) * | 1984-06-15 | 1986-01-25 | チバ‐ガイギー アクチエンゲゼルシヤフト | Manufacture of alpha,alpha-difluoroalkylphenyl ether and alpha-chloro-alpha-fluoroalkylphenyl ether and alpha-chloro-alpha-fluoroalkylphenyl ether derivative |
| JPH111468A (en) * | 1997-06-13 | 1999-01-06 | Mitsui Chem Inc | Production of diiodomethyl-p-toluylsulfone |
| JP2001348354A (en) * | 2000-06-05 | 2001-12-18 | Fuji Photo Film Co Ltd | Method for producing halomethane compound |
| JP2005511665A (en) * | 2001-11-29 | 2005-04-28 | ユニバーシティ・オブ・サザン・カリフォルニア | Preparation of fluorinated alkylsilanes mediated by magnesium |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009113362A1 (en) | 2008-03-10 | 2009-09-17 | セントラル硝子株式会社 | Method for producing oxygen-containing halogenated fluoride |
| US8105566B2 (en) | 2008-03-10 | 2012-01-31 | Central Glass Company, Limited | Method for producing oxygen-containing halogenated fluoride |
| WO2009147917A1 (en) | 2008-06-02 | 2009-12-10 | セントラル硝子株式会社 | Method for manufacturing oxygen-containing halogenated fluoride |
| CN102046521A (en) * | 2008-06-02 | 2011-05-04 | 中央硝子株式会社 | Method for manufacturing oxygen-containing halogenated fluoride |
| CN102046521B (en) * | 2008-06-02 | 2013-06-12 | 中央硝子株式会社 | Method for manufacturing oxygen-containing halogenated fluoride |
| WO2010100833A1 (en) * | 2009-03-02 | 2010-09-10 | 国立大学法人名古屋工業大学 | 2-fluoro-1,3-benzodithiol 1,1,3,3-tetraoxide derivatives, process for the preparation of same, and process for the preparation of monofluoromethyl-containing compounds using same |
| JP2010202539A (en) * | 2009-03-02 | 2010-09-16 | Nagoya Institute Of Technology | 2-fluoro-1,3-benzodithiol 1,1,3,3-tetraoxide derivative, method for producing the same and method for producing monofluoromethyl group-containing compound using the same |
| GB2480038A (en) * | 2009-03-02 | 2011-11-02 | Nagoya Inst Technology | 2-Fluoro-1,3-benzodithiol 1,1,3,3-tetraoxide derivatives, process for the preparation of same, and process for the preparation of monofluoromethyl-containing |
| US8558012B2 (en) | 2009-03-02 | 2013-10-15 | Nagoya Institute Of Technology | 2-fluoro-1,3-benzodithiol 1,1,3,3-tetraoxide derivative, production method thereof, and production method of monofluoromethyl group-containing compound using the same |
| GB2480038B (en) * | 2009-03-02 | 2014-01-08 | Nagoya Inst Technology | 2-Fluoro-1,3-benzodithiol 1,1,3,3-tetraoxide derivative, production method thereof, and production method of monofluoromethyl group-containing compound |
| JP2015078135A (en) * | 2013-10-15 | 2015-04-23 | 東ソ−・エフテック株式会社 | 1-bromo-1-fluorobis(phenylsulfonyl)methane, manufacturing method thereof and manufacturing method of 1-fluorobis(phenylsulfonyl)methane using the same |
Also Published As
| Publication number | Publication date |
|---|---|
| US7638654B2 (en) | 2009-12-29 |
| EP1992612A4 (en) | 2012-01-25 |
| JP4951754B2 (en) | 2012-06-13 |
| WO2007100074A1 (en) | 2007-09-07 |
| US20090131723A1 (en) | 2009-05-21 |
| EP1992612A1 (en) | 2008-11-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Reddy et al. | Synthesis and applications of sodium sulfinates (RSO 2 Na): a powerful building block for the synthesis of organosulfur compounds | |
| Durandetti et al. | Ni-catalyzed activation of α-chloroesters: a simple method for the synthesis of α-arylesters and β-hydroxyesters | |
| Alonso et al. | Carbon trifluoromethylation reactions of hydrocarbon derivatives and heteroarenes | |
| JP4951754B2 (en) | Fluorobis (arylsulfonyl) methane and process for producing the same | |
| Zeng et al. | Iron-catalyzed regio-and stereoselective chlorosulfonylation of terminal alkynes with aromatic sulfonyl chlorides | |
| Zhang et al. | Synthesis of pentafluorinated β-hydroxy ketones | |
| Wang et al. | Palladium-catalyzed Mizoroki–Heck-type reactions of [Ph 2 SR fn][OTf] with alkenes at room temperature | |
| Ge et al. | Electron Donor–Acceptor Complex Enabled Decarboxylative Sulfonylation of Cinnamic Acids under Visible-Light Irradiation | |
| Alonso et al. | 3, 5-Bis (trifluoromethyl) phenyl sulfones in the direct Julia− Kocienski olefination | |
| JP2001501954A (en) | Synthesis of aryl ethers, related methods and reagents | |
| Liang et al. | Aerobic Copper-Catalyzed Synthesis of (E)-Vinyl Sulfones by Direct C–S Bond Oxidative Coupling | |
| Yang et al. | Pd-catalyzed divergent trifluoroethylation and arylation of arylboronic acids by aryl (2, 2, 2-trifluoroethyl) iodonium triflates | |
| Zhu et al. | Copper-Catalyzed Bromodifluoroacetylative Cyclization of Enynes | |
| Xu et al. | Remote C–H Functionalization of 8-Aminoquinoline Ring | |
| CN101171223B (en) | Catalytic scriabine reaction | |
| JP2007063275A (en) | Allyl-type alkylation by iron catalyst action | |
| Bartels et al. | Diastereoselectivity of cyclopropanation of substituted α-fluorostyrenes versus styrenes by different methods | |
| EP1528053A1 (en) | Process for the preparation of (S)- or (R)-4-halo-3-hydroxybutyrates | |
| McKnight et al. | Carbofluorination of π‐Bonds and Related Reactions Involving Tandem C− C/C− F Bond Formation | |
| JP4744091B2 (en) | Process for producing optically active nitro compound and cyano compound | |
| Xu et al. | Cobalt (III)-Catalyzed and DMSO-Involved Allylation of 1, 3-Dicarbonyl Compounds with Alkenes | |
| JP2007203269A (en) | Asymmetric catalyst | |
| Monteiro | Organometallic Multicomponent Reactions | |
| Drinkel | Development of novel bissulfoxide and phosphine-olefin ligands for transition metal catalysis | |
| JP2007238525A (en) | METHOD FOR PRODUCING OPTICALLY ACTIVE beta-HYDROXYIMINE COMPOUND |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20090216 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111115 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111215 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120214 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 4951754 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313114 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313115 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S531 | Written request for registration of change of domicile |
Free format text: JAPANESE INTERMEDIATE CODE: R313531 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |